This is a competitive renewal application for the Harvard Brain Tissue Resource Center, a national resource for the acquisition, processing, storage and distribution of high quality postmortem (PM) brain to the neuroscience community. This facility collects brains from normal controls (CON), as well as individuals with a variety of movement disorders (Huntington's chorea and Parkinson's disease), dementias (Alzheimer's disease, frontotemporal dementias) and major psychoses (schizophrenia and bipolar disorders). The HBTRC distributes tissue specimens to neuroanatomists, neuropathologists, neuropharmacologists, neurochemists and molecular biologists throughout the U.S. Over the past 5 years, this tissue has contributed to more than 170 scientific publications. During the current funding period, the HBTRC has undergone a major restructuring that has resulted in an increase in the overall quality and efficiency of its operation. An important outcome of this re-organization has been an increase in the number of fresh, frozen cases and a marked decrease in the postmortem interval (PMI). As a result of this effort, abundant, high quality tissue is now available for a broad array of state-of-the-art research applications. The number of CONs received by the HBTRC has more than doubled during the current funding period and the HBTRC is now able to provide investigators with sets of CONs and diseased brains matched for age, PMI, gender and hemisphere. For the major psychoses, where the acquisition of postmortem brains is actually challenging, the number of schizophrenic and bipolar cases has also increased. Since these are largely from community-based referrals, the potential confounding effects of institutionalization, inanition and substance abuse are relatively lower than in medical examiner cases. To facilitate the donation process, the HBTRC has established a website with a) Informed Consent forms for potential donors and their families, b) instructions for handling brains by pathologists or dieners involved in brain removal, and c) application forms for investigators seeking tissue for their research. The HBTRC has also developed a User-Interactive Database, so that investigators who receive tissue from the "bank" can obtain demographics, neuropathology reports and images of gross dissections and histological slides for their cases. With supplemental funding from NIH, the HBTRC is now obtaining gene expression profiling and SNP analyses using the standard Affymetrix microarray system and this information will be immediately placed in our public domain National Databank as it is obtained. All investigators receiving tissue from the HBTRC will also be encouraged to "deposit" their findings in the Databank so that they will be available to the neuroscience community for complex relational analyses. Over the next funding period, these new initiatives will enhance the functioning of the "brain bank" in its role as a vital national resource.